Effect of Hydroxyurea Therapy on Growth Parameters in Older Children (6-15 Year-Old) with Sickle Cell Disease: Low Dose Versus High Dose.

Growth impairment is a known complication of sickle cell disease (SCD). Few studies explored the potential effects of hydroxyurea (HU) on growth in children with SCD in relation to HU dose and response. This is a prospective study conducted at Sultan Qaboos University Hospital, Oman, and included 91 SCD patients with age below 16 years when started on HU, aiming to explore the potential effect/s of HU on growth parameters of older children with SCD in relation to their clinical improvement and the dose required for this improvement. Weight, height, and body mass index (BMI) were collected at baseline, 6 and 18 months after initiation. Anthropometric data were compared to WHO standards. Initial height and BMI Z scores (HAZ and WAZ) were lower compared to WHO norms. HAZ and WAZ did not change significantly after 6 and 18 months on HU therapy. However, BMI Z-scores improved significantly after 6 and 18 months of follow-up (p value 0.044 and 0.028 respectively). No significant changes were observed in WAZ or HAZ among patients on low dose versus those on high dose. BMI Z score improved significantly after 18 months of low dose group (p = 0.014) but did not change in those on high dose HU. In conclusion, HU therapy did not adversely affect weight and height growth in older children with SCD. BMI Z scores improved at 18 months in patients on low dose but not in those on high dose (p = 0.014).

Cardio-protective effect of regular transfusion in children with non-transfusion dependent thalassemia (NTDT): A cohort study.

BACKGROUND AND AIM OF THE WORK: Cardiac complications occur in patients with non-transfusion dependent thalassemia (NTDT). The study aimed to evaluate transfusion effect on systolic and diastolic cardiac function in young NTDT patients.  Methods:  Study design: Cohort study. Seventeen regularly-transfused patients with NTDT (12.5±5.3 years; group 1) and 15 none/minimally transfused patients (13.2±4.8 years; group 2) were followed up for 5 years and compared as regards their clinical parameters, echocardiographic and Tissue-Doppler-Imaging. RESULTS: Group 2 patients had significantly higher peak late-diastolic velocity of the left-ventricular-inflow Doppler (Am). Mitral-valve A-wave duration/pulmonary-veins, A-wave duration-ratio and pulmonary-vein S/D velocities-ratio were larger in group 2 as well (p = < 0.01). The diameters of right and left outflow-tract were larger with a higher cardiac-index in patients of group 2. Systolic-function was similar in the 2 studied groups. CONCLUSION: Diastolic function assessment revealed indicators of an abnormal relaxation of left-ventricle in non-transfused patients, which suggests a diastolic dysfunction. An increase in the diameter of the outflow-tract is likely attributed to high cardiac-output status in non-transfused NTDT patients as they have a higher cardiac index. Early start of regular transfusion for NTDT patients might prevent serious long-term cardiac complications.

Incorporation of Evidence-based Guidelines on Bleeding Risk Assessment Prior to Surgery into Practice: Real-time Experience.

Objectives: Despite guidelines recommending no need for coagulation testing before surgeries when a history of bleeding is negative, surgeons still overuse it in this part of the world. We aim to measure unbiased estimates of hemostatic outcomes in ear, nose, and throat (ENT) surgeries and assess the surgeons' behavior of preoperative coagulation testing. Methods: We enrolled all patients who underwent ENT surgeries from July 2017 to January 2018. The primary outcome was postoperative bleeding. Surgeons were asked about their decision on history alone or doing coagulation testing and their reason. Results: We recruited 730 patients; 372 were interviewed for a challenging bleeding history alone (group 1), and 358 had preoperative coagulation testing (group 2). Coagulation testing was repeated twice or more in 55.0% of patients, and more than half had coagulation factor and Von Willebrand factor assays. Most surgeons performed coagulation testing because of habitual practice. Conclusions: Almost half of the local surgeons consider coagulation testing as standard to evaluate bleeding risk before surgical procedures. This resulted in unnecessary delays in surgeries, parent/patient anxiety, and additional total cost. We recommend awareness campaigns for surgeons and the involvement of surgical societies to adhere to guidelines of detailed hemostatic history.

Age of Transition Readiness of Adolescents and Young Adults With Chronic Diseases in Oman: Need an Urgent Revisit.

BACKGROUND: The Ministry of Health in Oman and some of Gulf regions set the cut-off age of "transfer" from child health care to adult health care at 13 years of age. Within the existing health system in this part of the world, there is paucity of evidence on the appropriate age for health care "transfer" of adolescents and young adults to adult health care. Similarly, there is lack of a structured health care "transition" program. The objective of the study is to indirectly determine the appropriateness of present cut-off age of transfer by studying readiness for transition among Omani patients suffering from chronic hematological conditions. METHODS: One hundred fifty adolescents and young adults with chronic hematological conditions were recruited from pediatric and adults clinics at Sultan Qaboos University Hospital. Participants were interviewed by a trained research assistant using the Arabic version of UNC TRxANSITION Scale to assess self-management skills and health related knowledge for transition. The score range is 0 to 10; the transition readiness of the patients is assessed as low (0 to 4), moderate (4 to 6), and high (6 to 10) respectively. The continuous variables were analyzed by parametric or nonparametric methods as appropriate. χ2 analysis was done to determine association of age groups within each sexes. RESULTS: The study recruited 150 subjects (52.7% males) with 50 patients in each of the 3 age groups of 10 to 13 years (lower), 14 to 17 years (middle), and 18 to 21years (higher). The mean UNC TRxANSITION Scale scores of 5.14 (SD=1.27) in males in the total sample were significantly lower as compared with that of 5.67 (SD=1.50) in females (P=0.022). There is a steady increase in the overall median score with increase in age group, with median score of 4.42 in the lower, 5.26 in the middle and 6.81 in the higher age group (P<0.001). In section wise analysis, except for Adherence and Nutrition sections of the scale, all sections have statistically significant difference in the median scores across various age categories with lowest scores in the 10 to 13 age group and highest scores in the 18 to 21 years group. In the section related to reproduction, females had significantly higher mean ranks (31.52) and compared with 17.19 in males (P=0.001). The overall median transition score when analyzed separately for males and females across age groups showed that in the higher age group, 67% of males (P=0.008) and 90% females (P<0.001) have high transition scores compared with the other 2 groups. CONCLUSIONS: Higher age was a significant predictor for transition readiness with median score being "moderate" in the lower and middle age groups, while the higher age groups scoring "high" on transition readiness. However, in the higher age group, the females (90%) showed better transition readiness than males (67%). The current age of transfer of 13 years is just at "moderate" levels. We recommend the need for establishing transition preparation program in Oman; increasing health transfer age in Oman to a cut-off age of 18 years and taking sex differences into consideration when providing interventions.

Rare inherited coagulation disorders in young children in Oman.

Background: Rare coagulation disorders represent 3-5% of all inherited coagulation deficiencies and are usually inherited as autosomal recessive. Oman has high rate of consanguineous marriages; we aimed to study the prevalence, presentation and management in affected Omani children. Materials and Methods: Retrospective study in pediatric patients with rare coagulation disorders in a tertiary hospital in Oman from 2009 to 2020. Results: Rare coagulation disorders were diagnosed in 79 patients (39 males/40 females), aged 1 day to 13 years, accounting for 24.7% (79/319) of all children with inherited coagulation disorders; remainder included patients with hemophilia and von Willebrand disease. FXI deficiency was most common with prevalence of 39.2%, followed by fibrinogen disorders 32.9%, FVII 18.9%, FV 5%, FXIII 2.5%, and FX deficiencies 1.2%. Manifestations ranged from mild to serious to rare/atypical; presentation at birth, ruptured-hemorrhagic ovarian cyst, splenic laceration-rupture, and sight-threatening retrobulbar-intraocular hemorrhage. Intracranial hemorrhage (ICH) occurred in 9/79 patients, it was initial mode of presentation in seven of them. Global developmental delay as a complication occurred in three. Standardized treatment strategies were used with prophylaxis initiation early in life in severely affected children. Conclusions: This ethnic group demonstrated unique features in terms of: heterogenous/atypical presentations; severe manifestations in moderate phenotype hypofibrinogenemia; clinical severity and laboratory phenotype correlation in FV deficiency; poor association between factor activity level and bleeding severity in FVII deficiency and severe bleeding tendency despite moderate laboratory phenotype in FXIII deficiency. We recommend multicenter collaboration to identify the genotype-phenotype correlation and therapeutic options of such rare, yet serious disorders.

Clinical and molecular characteristics of imerslund-gräsbeck syndrome: First report of a novel Frameshift variant in Exon 11 of AMN gene.

INTRODUCTION: Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal-recessive disorder characterized by selective vitamin B12 malabsorption, megaloblastic anemia, and proteinuria. The precise incidence of this disorder is unknown in the Middle East and Arab countries. The disease is caused by a homozygous variant in either AMN or CUBN genes. In addition, some compound heterozygous variants are reported. METHODS: Clinical and laboratory data of patients diagnosed with IGS in Oman were retrospectively collected. Mutation analysis for all genes involved in vitamin B12/folic acid metabolism and megaloblastic anemia was conducted using next-generation sequencing (NGS). RESULTS: Three siblings (2 girls and a boy) have been diagnosed with the condition. They exhibit a phenotypic variability with different age of presentation and different spectrum of disease. All patients harbor a novel biallelic frameshift mutation in exon 11 of AMN gene (p.Pro409Glyfs*), which was not reported previously in the literature. Both parents are heterozygotes for the same variant. All patients responded well to vitamin B12 parenteral therapy, but proteinuria persisted. CONCLUSION: In communities with high incidence of consanguinity, cases of early-onset vitamin B12 deficiency should be thoroughly investigated to explore the possibility of Imerslund-Gräsbeck syndrome and other vitamin B12-related hereditary disorders. Further local and regional studies are highly recommended.

Outcome of Early Hemostatic Intervention in Children With Sepsis and Nonovert Disseminated Intravascular Coagulation Admitted to PICU: A Randomized Controlled Trial.

OBJECTIVES: Evaluation of the outcome of early hemostatic management of disseminated intravascular coagulopathy in patients with severe sepsis/septic shock admitted to PICU, before the development of clinically overt disseminated intravascular coagulopathy. DESIGN: Prospective interventional, open label randomized controlled clinical trial. SETTING: PICU at Alexandria University Children's Hospital. PATIENTS: The study included 80 patients with proven severe sepsis/septic shock in nonovert disseminated intravascular coagulopathy stage. They were randomly assigned into two groups (group 1 and group 2). INTERVENTIONS: Specific intervention was applied for group 1 (plasma transfusion, low-dose unfractionated heparin, and tranexamic acid). MEASUREMENTS: All patients had assessment of Pediatric Index of Mortality 2 score, Pediatric Logistic Organ Dysfunction score, inotropic score, routine laboratory, and hemostatic tests including fibrin degradation products and d-dimers. Disseminated intravascular coagulopathy risk assessment scores were calculated on daily basis. RESULTS: Mortality rate was significantly higher in group 2. Progression to overt disseminated intravascular coagulopathy was significantly more common among group 2 patients than group 1 (45% and 10%, respectively) (p < 0.0001). Disseminated intravascular coagulopathyRisk Assessment Scores were significantly higher on the second and fifth days among group 2 patients. The initial specific hemostatic intervention was the only significant predictor of survival and prevention of progression to overt disseminated intravascular coagulopathy. CONCLUSIONS: Our results suggest that early use of a combination of fresh frozen plasma transfusion, low-dose heparin, and tranexamic acid in children with severe sepsis/septic shock in the "window of opportunity" before the development of overt disseminated intravascular coagulopathy stage was associated with better outcome for survival and prevention of progression to overt disseminated intravascular coagulopathy, with no increase in bleeding risk. Larger multicenter studies are needed to further prove this practice.

Preoperative transfusion versus no transfusion policy in sickle cell disease patients: a randomized trial.

BACKGROUND: Many children with sickle cell disease (SCD) indicated for adenotonsillectomy receive pre-operative transfusion therapy, either simple or exchange transfusion, in order to reduce surgical and sickle cell disease-related complications. SUBJECTS AND METHODS: This is a prospective randomized controlled clinical trial aiming to compare between preoperative simple transfusion and no transfusion in pediatric patients with sickle SCD admitted in Sultan Qaboos University Hospital, Muscat, Oman for adenotonsillectomy during the period from January 2014 through June 2018. They were randomly assigned into two arms (simple transfusion and no transfusion). RESULTS: Postoperative SCD-related complications have been encountered in 6 out of 138 patients (4.3%). There was no statistically significant difference between the two studied groups as regards the development of surgical or SCD-related complications (p = 0.6 and 0.8 respectively). The length of postoperative hospital stay was comparable in the two groups. (p = 0.607). SCD-related complications occurred exclusively in cases with homozygous sickle anemia (4 out of 81 = 4.9%). CONCLUSION: Sickle cell disease patients with a hemoglobin level above 7.5 g/dL do not need PRBCs transfusion prior to adenotonsillectomy. This approach did not increase the risk of postoperative surgical or SCD-related complications.

Sepsis-related anemia in a pediatric intensive care unit: transfusion-associated outcomes.

BACKGROUND: Pediatric patients with sepsis in intensive care units are at high risk of developing anemia, which might have adverse effects on their prognosis. This study aimed to evaluate the impact of red blood cell (RBC) transfusion on the outcomes of patients admitted to a pediatric intensive care unit (PICU) with sepsis. METHODS: We conducted a prospective randomized clinical trial, enrolling 67 children, aged 2 to 144 months who were admitted to a PICU with a new episode of sepsis from November 2017 to April 2018. Patients were allocated randomly to two groups: Group 1, liberal transfusion strategy group, including 33 patients who had initial hemoglobin (Hb) between 7 or greater and less than 10 g/dL and received an RBC top-up transfusion to 12 g/dL; and Group 2, restrictive strategy group, including 34 patients who had the same Hb range and did not receive RBCs. Patients with Hb less than 7 or greater than 10 g/dL were excluded. RESULTS: Of 33 patients who received liberal transfusions, 31 (93.94%) required ventilation, and 29 (87.88%) had multiorgan dysfunction. They had a significantly lengthier hospital stay and a higher incidence of acute respiratory distress syndrome and acute lung injury. Moreover, mortality was significantly higher in the liberal transfusion group (42.4% vs. 17.6%). CONCLUSIONS: Compared to the restrictive transfusion strategy, liberal transfusion might be associated with a worse outcome. However, the possible role of other known and unknown confounding factors and minor protocol violations should be taken into consideration. We recommend minimizing factors worsening anemia in PICU patients to reduce the need for transfusion.

Pulmonary Artery Pseudoaneurysm in a Child With ß-Thalassemia Major.

Pulmonary artery aneurysms and pseudoaneurysms are rare vascular anomalies in children that can lead to massive hemoptysis resulting in severe morbidity and even mortality. High level of clinical suspicion, timely diagnosis, and prompt management are important for a better outcome. Here, we report a case of a 14-year-old adolescent with ß-thalassemia major who presented with life-threatening hemoptysis due to pulmonary artery pseudoaneurysm and was successfully treated with coil embolization.

Evaluation of endocrine complications in beta-thalassemia intermedia (ß-TI): a cross-sectional multicenter study.

BACKGROUND: Data on the prevalence and type of endocrine disorders in ß-thalassemia intermedia (ß-TI) patients are scarce. This multicenter study was designed to determine the prevalence of endocrine complications and the associated risk factors in a large group of ß-TI patients. METHODS: In this cross-sectional multicenter study, 726 ß-TI patients, aged 2.5-80 years, registered at 12 thalassemic centers, from nine countries, were enrolled during 2017. In a subgroup of 522 patients (mean age 30.8 ± 12.1; range: 2.5-80 years) from Qatar, Iran, Oman, Cyprus, and Jordan detailed data were available. RESULTS: Overall, the most prevalent complications were osteopenia/osteoporosis (22.3%), hypogonadism (10.1%), and primary hypothyroidism (5.3%). In the subgroup multivariate analysis, older age was a risk factor for osteoporosis (Odds ratio: 7.870, 95% CI: 4.729-13.099, P < 0.001), hypogonadism (Odds ratio: 6.310, 95% CI: 2.944-13.521, P < 0.001), and non-insulin-dependent diabetes mellitus (NIDDM; Odds ratio: 17.67, 95% CI: 2.217-140.968, P = 0.007). Splenectomy was a risk factor for osteoporosis (Odds ratio: 1.736, 95% CI: 1.012-2.977, P = 0.045). Hydroxyurea was identified as a "protective factor" for NIDDM (Odds ratio: 0.259, 95% CI: 0.074-0.902, P = 0.034). CONCLUSIONS: To the best of our knowledge, this is the largest cohort of ß-TI patients with endocrine disorders evaluated in extremely heterogenic thalassemic populations for age, clinical, hematological, and molecular composition. The study demonstrates that endocrine complications are less common in patients with ß-TI compared with ß-TM patients. However, regular monitoring with timely diagnosis and proper management is crucial to prevent endocrine complications in ß-TI patients.

Elevated levels of circulating invariant natural killer cell subsets are skewed toward Th2-like phenotype in children with sickle cell disease.

Invariant natural killer T (iNKT) cells are being considered as potential targets for immunotherapeutic strategies in a variety of conditions including sickle cell disease (SCD). However, relatively little is known about the fate of iNKT cell subsets in children with SCD. Herein, quantitative and qualitative analyses of circulating iNKT cell subsets were carried out in 120 children in steady state and 30 healthy controls. Children with SCD displayed significantly elevated levels of circulating iNKT cell subsets with a preferential polarization toward Th2-like cells. The known SCD modifiers did not influence levels of iNKT cell subsets, except that children carrying the Bantu haplotype exhibited elevated levels of CD4iNKT cells, and to a lesser degree CD8iNKT cells. Collectively, these findings indicate that circulating iNKT cell subsets are significantly increased in children with SCD, and highlight the existence of imbalanced production of cytokines toward Th2-like phenotype, which seems to be associated with genetic polymorphisms.

Hemoglobin F as a predictor of health-related quality of life in children with sickle cell anemia.

PURPOSE: As treatment options for children with sickle cell anemia (SCA) continue to expand survival, evaluation of factors associated with health-related quality of life (HRQoL) is becoming an important aspect for further improving clinical management. Although the general features of SCA are similar, factors influencing HRQoL within a country may differ from those of other countries, therefore this study aimed to explore factors affecting HRQoL in children with SCA living in the Sultanate of Oman. METHODS: This was a cross-sectional study in which the PedsQL™ Sickle Cell Disease Module was used to evaluate the overall HRQoL in children with SCA. The socio-demographic data, clinical, and treatment outcomes were collected. Univariate and multivariate linear regression analyses were used to identify predictors of HRQoL. RESULTS: A total of 123 children with SCA, aged from 2 to 16 years were enrolled. The mean total HRQoL score was 52 ± 15% (9-94), where Worry II scale recorded the highest score. The multiple regression analysis revealed that the only predictors of total HRQoL score were hemoglobin F (B = 0.64, 95% confidence interval [CI] 0.149-1.118, P = 0.009) and to a lesser degree white blood cell count (B = - 0.99, 95% CI - 1.761 to - 0.198, P = 0.01), independently of other study parameters such as age, gender, spleen status, and hydroxyurea therapy. CONCLUSIONS: Collectively, these findings indicated that hemoglobin F out-weighted white blood cell count in predicting HRQoL in Omani children with SCA. Recognition of these factors could help health professionals to develop effective strategies to improve the overall HRQoL in these young patients.

Synergistic Effect of Newly Introduced Root Canal Medicaments; Ozonated Olive Oil and Chitosan Nanoparticles, Against Persistent Endodontic Pathogens.

This study was conducted to investigate the antimicrobial-biofilm activity of chitosan (Ch-NPs), silver nanoparticles (Ag-NPs), ozonated olive oil (O3-oil) either separately or combined together against endodontic pathogens. While testing the antimicrobial activity, Ch-NPs showed the least minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values exerting eightfold higher bactericidal activity than O3-oil against both Enterococcus faecalis and Streptococcus mutans as well as fourfold higher fungicidal activity against Candida albicans. Antimicrobial synergy test revealed synergism between O3-oil and Ch-NPs against the test pathogens (FIC index ≤ 0.5). Ch-NPs was superior at inhibiting immature single and mixed-species biofilm formations by 97 and 94%, respectively. Both of O3-oil and Ch-NPs had a complete anti-fibroblast adherent effect. The safety pattern results showed that O3-oil was the safest compound, followed by Ch-NPs. The double combination of Ch-NPs and O3-oil reduced the mature viable biofilm on premolars ex vivo model by 6-log reductions, with a fast kill rate, indicating potential use in treating root canals. Therefore, the double combination has the potential to eradicate mature mixed-species biofilms and hence it is potent, novel and safe.

An ICET- A survey on Hypoparathyroidism in Patients with Thalassaemia Major and Intermedia: A preliminary report.

Hypoparathyroidism (HPT) is a rare disease with leading symptoms of hypocalcemia, associated with high serum phosphorus levels and absent or inappropriately low levels of parathyroid hormone (PTH). In patients with thalassemias it is mainly attributed to transfusional iron overload, and suboptimal iron chelation therapy. The main objectives of this survey were to provide data on the prevalence, demographic and clinical features of HPT in thalassemia major (TM) and intermedia (TI) patients living in different countries, and to assess its impact in clinical medical practice. A questionnaire was sent to all Thalassemia Centres participating to the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A) Network.Seventeen centers, treating a total of 3023 TM and 739 TI patients, participated to the study. HPT was reported in 206 (6.8%) TM patients and 33 (4.4%) TI patients. In general, ages ranged from 10.5 to 57 years for the TM group and from 20 to 54 years for the TI group. Of the 206 TM patients and 33 TI patients with HPT, 117 (48.9%) had a serum ferritin level >2.500 ng/ml (54.3% TM and 15.1% TI patients) at the last observation. Hypocalcemia varied in its clinical presentation from an asymptomatic biochemical abnormality to a life-threatening condition, requiring hospitalization. Calcium and vitamin D metabolites are currently the cornerstone of therapy in HPT. In TM patients, HPT was preceded or followed by other endocrine and non-endocrine complications. Growth retardation and hypogonadism were the most common complications (53.3% and 67.4%, respectively). Although endocrine complications were more common in patients with TM, non-transfused or infrequently transfused patients with TI suffered a similar spectrum of complications but at a lower rate than their regularly transfused counterparts.In conclusion, although a large international registry would help to better define the prevalence, comorbidities and best treatment of HPT, through the result of this survey we hope to give a clearer understanding of the burden of this disease and its unmet needs. HPT requires lifelong therapy with vitamin D or metabolites and is often associated with complications and comorbidities.Therefore, it is important for endocrinologists and other physicians, who care for these patients, to be aware of recent advances of this disorder.

Regulatory B Cells Are Functionally Impaired in Patients Having Hemophilia A With Inhibitors.

Development of inhibitors remains a major clinical complication in patients with hemophilia A receiving replacement therapy with factor VIII (FVIII). Understanding the immune mechanisms involved in the development of inhibitors can provide valuable information about pathways to human tolerance. Recent evidence indicates that B regulatory (Breg) cells play a pivotal role in controlling the production of antibodies (Abs) while promoting follicular T helper (Tfh) cells and monocytes, expressing the low-density lipoprotein receptor-related protein (LRP/CD91), which is involved in FVIII intake from the circulation. We studied circulating levels of Breg cells along with Tfh cells and the expression of LRP/CD91 on monocytes in patients with hemophilia A using 8-color flow cytometry and cell culture. Compared to healthy controls, patients with hemophilia A with inhibitors showed a severe reduction in levels of Breg cells and produced less interleukin-10 when activated via the CD40 signaling pathway. In addition, patients with hemophilia A with inhibitors exhibited an overexpression of LPR/CD91 on monocytes and normal levels of Tfh cells. Levels of Breg cells were not significantly related to LPR/CD91 although negative associations were evidenced. Collectively, these results provide new insights into the role of Breg cells and LPR/CD91 in the development of inhibitors in patients with hemophilia A.

Vincristine-induced neuropathy in pediatric patients with acute lymphoblastic leukemia in Oman: Frequent autonomic and more severe cranial nerve involvement.

BACKGROUND: Vincristine (VCR) induced peripheral neuropathy is a common complication in children with acute lymphoblastic leukemia (ALL). PROCEDURES: A retrospective data analysis over an interval of 10 years (2006-2016) of all children with ALL seen at Sultan Qaboos University Hospital was carried out. Electronic medical records of eligible patients were reviewed. Patients with clinical evidence of neuropathy and abnormal nerve conduction studies (NCSs) were included in the study. RESULTS: Nineteen (nine females and 10 males) out of 103 pediatric patients developed VCR-related neuropathy, and their age ranged between 2.5 and 14 years. Symptoms started after 2-11 doses of VCR. All 19 patients had documented peripheral neuropathy on NCSs. The autonomic nervous system and cranial nerves affection was relatively common in our patients; two presented with bradycardia, two patients with unexplained tachycardia, and five had abdominal pain and constipation, complicated by typhlitis in two patients. One patient developed unilateral hearing loss. Two patients developed severe life-threatening cranial nerve involvement with bilateral ptosis and recurrent laryngeal nerve involvement presented as vocal cord paralysis, hoarseness of voice, frequent chocking, and aspiration episodes. CONCLUSIONS: Peripheral neuropathy was the commonest form of VCR-related neuropathy. Autonomic neuropathy was relatively common in our patients. Cranial neuropathy is a serious side effect of VCR that can be severe, involving multiple cranial nerves and needs prompt recognition and management. Concomitant administration of pyridoxine and pyridostigmine does not seem to protect against further neurological damage in some patients.

Efficacy and Safety of Dapsone Versus Trimethoprim/Sulfamethoxazol for Pneumocystis Jiroveci Prophylaxis in Children With Acute Lymphoblastic Leukemia With a Background of Ethnic Neutropenia.

STUDY OBJECTIVE: To study dapsone in comparison with trimethoprim/sulfamethoxazole (TMP/SMX) for Pneumocystis jiroveci (PJP) prophylaxis in children with acute lymphoblastic leukemia (ALL). DESIGN: A retrospective study with a prospective follow-up. PATIENTS: Pediatric ALL patients diagnosed between May 2009 and May 2014, who are still receiving or have completed their maintenance chemotherapy. Patients who completed chemotherapy were prospectively followed up for neutropenia. METHODS: TMP/SMX was used as the initial PJP prophylaxis. An alternative drug was indicated if the patient remained cytopenic for >3 weeks. Average absolute neutrophilic count (ANC), average % of oral mercaptopurine (6-MP), and methotrexate doses were calculated over a period of 6 months before and after shifting to dapsone. RESULTS: Sixty-two ALL patients were eligible for analysis. Twenty-four patients (38.7%) received TMP/SMX for PJP prophylaxis, whereas 34 patients received Dapsone (54.8%). Only 3 patients received IV pentamidine (4.8%), whereas 1 patient (1.6%) received atovaquone. The incidence of prophylaxis failure was 1/1041 months on TMP/SMX and 1/528 months on dapsone. After shifting to dapsone, patients maintained significantly higher ANC (1.46±0.46 vs. 1.17±0.40, P=0.0053), and received significantly higher doses of 6-MP (62.61%±11.45 vs. 57.45±10.14, P=0.0081) and methotrexate (64.9%±14.29 vs. 56.5%±9.9, P=0.0176), with a significantly shorter duration of chemotherapy interruption (1.94±1.2 vs. 3.25±1.29 wk, P=0.0002). CONCLUSIONS: Dapsone for PJP prophylaxis in ALL allowed patients to maintain higher ANC and to receive higher doses of chemotherapy, while maintaining a low incidence of PJP breakthrough infection.

Review and Recommendations on Management of Adult Female Thalassemia Patients with Hypogonadism based on Literature Review and Experience of ICET-A Network Specialists.

BACKGROUND: Multi-transfused thalassemia major (TM) patients frequently develop severe endocrine complications, mainly due to iron overload, anemia, and chronic liver disease, which require prompt diagnosis, treatment and follow-up by specialists. The most common endocrine complication documented is hypogonadotropic hypogonadism which increases with age and associated comorbidities. It is thus important for physicians to have a clear understanding of the pathophysiology and management of this disorder. Also to be aware of the side effects, contraindications and monitoring of sex steroid therapy. In this paper, practical ICET-A recommendations for the management of hypogonadism in adult females with TM are addressed. METHODS: In March 2015, the Coordinator of the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescent Medicine (ICET-A) conducted a two-step survey to assess the attitudes and practices of doctors in the ICET-A network taking care of adult female TM patients with hypogonadism. They were clinically characterized by the absence of pubertal development or discontinuation or regression of the maturation of secondary sex characteristics, and biochemically by persistent low FSH, LH and estradiol levels. Recently a supplementary survey on adult female hypogonadism in TM was undertaken within the ICET-A network. RESULTS: The completed questionnaires were returned by 16 of 27 specialists (59.2%) following 590 female TM patients over the age of 18 years; 315 patients (53.3%) had hypogonadism, and only 245 (74.6%) were on hormone replacement therapy (HRT). Contraceptive oral pills (COC) were the first treatment choice in 11 centers (68.7%). A wide range of COCs was used with different progestin contents. In general, the patients' compliance to treatment was reported as good in 81.2 % of centers. The frequency of required tests for follow-up HRT, in addition to the regular check-up for thalassemia, was variable in the participating centers. CONCLUSIONS: Doctors taking care of TM patients should have sound knowledge of the pathophysiology of hypogonadism in adult females with TM. They should know the potential effects of HRT including advantages and disadvantages of estrogen and progestins. Moreover, they should keep in consideration the emotional needs of these patients dreaming of attaining a full pubertal development.